Claudin 18.2 (CLDN18) as a Radioligand Therapy Target
Claudin 18.2 (CLDN18), claudin 18, is a cell-surface protein. In Human Protein Atlas immunohistochemistry, Claudin 18.2 staining is highest in gastric cancer (50% of samples positive), ovarian cancer (33% of samples positive) and pancreatic cancer (40% of samples positive). Evidence on whether Claudin 18.2 internalizes is mixed. Clinical status: Discovery-stage (no clinical drug program).
Is Claudin 18.2 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ⚠️ Tumor expression: Medium IHC staining in gastric cancer, 50% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
Claudin 18.2 expression in cancer
Protein expression of Claudin 18.2 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Gastric Cancer | 0.44 | Medium | 50% |
| Ovarian Cancer | 0.33 | Medium | 33% |
| Pancreatic Cancer | 0.30 | Medium | 40% |
| Lung Cancer | 0.24 | Medium | 27% |
| Liver Cancer | 0.22 | Medium | 22% |
| Testicular Cancer | 0.12 | Low | 27% |
| Colorectal Cancer | 0.11 | Low | 17% |
| Cervical Cancer | 0.08 | Low | 8% |
| Glioma | 0.06 | Low | 8% |
| Melanoma | 0.03 | Low | 8% |
Not detected by IHC in: skin cancer, head and neck cancer, lymphoma, breast cancer, kidney cancer, thyroid cancer, bladder cancer, neuroendocrine tumors, prostate cancer, endometrial cancer.
Is Claudin 18.2 internalized?
Uncertain. The abstract mentions mechanisms of resistance including "impaired internalization," but does not provide clear evidence that CLDN18 undergoes receptor internalization or endocytosis upon binding.
Sources: PMID 42225587 · PMID 42168932 · PMID 42095384 · PMID 41484653 · PMID 40594106. AI-extracted from abstracts, so verify before citing.
Claudin 18.2 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for Claudin 18.2 yet. Search ClinicalTrials.gov for Claudin 18.2 trials.
Claudin 18.2 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See Claudin 18.2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
Claudin 18.2 gene essentiality (DepMap)
CRISPR knockout effect across 1249 cancer cell lines: -0.04 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related gastric cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · FAP · EGFR · SSTR2 · CEA (CEACAM5) · Mesothelin (MSLN) · STEAP2
See all radioligand therapy targets in gastric cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.